Future wave climate over the west-European shelf seas

In this paper, we investigate changes in the wave climate of the west-European shelf seas under global warming scenarios. In particular, climate change wind fields corresponding to the present (control) time-slice 1961–2000 and the future (scenario) time-slice 2061–2100 are used to drive a wave generation model to produce equivalent control and scenario wave climate. Yearly and seasonal statistics of the scenario wave climates are compared individually to the corresponding control wave climate to identify relative changes of statistical significance between present and future extreme and prevailing wave heights. Using global, regional and linked global–regional wind forcing over a set of nested computational domains, this paper further demonstrates the sensitivity of the results to the resolution and coverage of the forcing. It suggests that the use of combined forcing from linked global and regional climate models of typical resolution and coverage is a good option for the investigation of relative wave changes in the region of interest of this study. Coarse resolution global forcing alone leads to very similar results over regions that are highly exposed to the Atlantic Ocean. In contrast, fine resolution regional forcing alone is shown to be insufficient for exploring wave climate changes over the western European waters because of its limited coverage. Results obtained with the combined global–regional wind forcing showed some consistency between scenarios. In general, it was shown that mean and extreme wave heights will increase in the future only in winter and only in the southwest of UK and west of France, north of about 44–45° N. Otherwise, wave heights are projected to decrease, especially in summer. Nevertheless, this decrease is dominated by local wind waves whilst swell is found to increase. Only in spring do both swell and local wind waves decrease in average height

Duration of Treatment for Pseudomonas aeruginosa Bacteremia : a Retrospective Study

Introduction: There is no consensus regarding optimal duration of antibiotic therapy for Pseudomonas aeruginosa bacteremia. We aimed to evaluate the impact of short antibiotic course. Methods: We present a retrospective multicenter study including patients with P. aeruginosa bacteremia during 2009-2015. We evaluated outcomes of patients treated with short (6-10 days) versus long (11-15 days) antibiotic courses. The primary outcome was a composite of 30-day mortality or bacteremia recurrence and/or persistence. Univariate and inverse probability treatment-weighted (IPTW) adjusted multivariate analysis for the primary outcome was performed. To avoid immortal time bias, the landmark method was used. Results: We included 657 patients; 273 received a short antibiotic course and 384 a long course. There was no significant difference in baseline characteristics of patients. The composite primary outcome occurred in 61/384 patients in the long-treatment group (16%) versus 32/273 in the short-treatment group (12%) (p = 0.131). Mortality accounted for 41/384 (11%) versus 25/273 (9%) of cases, respectively. Length of hospital stay was significantly shorter in the short group [median 13 days, interquartile range (IQR) 9-21 days, versus median 15 days, IQR 11-26 days, p = 0.002]. Ten patients in the long group discontinued antibiotic therapy owing to adverse events, compared with none in the short group. On univariate and multivariate analyses, duration of therapy was not associated with the primary outcome. Conclusions: In this retrospective study, 6-10 days of antibiotic course for P. aeruginosa bacteremia were as effective as longer courses in terms of survival and recurrence. Shorter therapy was associated with reduced length of stay and less drug discontinuation

Interleukin-1 Receptor-Associated Kinase-3 Is a Key Inhibitor of Inflammation in Obesity and Metabolic Syndrome

BACKGROUND: Visceral obesity is associated with the rising incidence of type 2 diabetes and metabolic syndrome. Low-grade chronic inflammation and oxidative stress synergize in obesity and obesity-induced disorders. OBJECTIVE: We searched a cluster of molecules that support interactions between these stress conditions in monocytes. METHODS: RNA expressions in blood monocytes of two independent cohorts comprising 21 and 102 obese persons and 46 age-matched controls were determined by microarray and independently validated by quantitative RT-PCR analysis. The effect of three-month weight loss after bariatric surgery was determined. The effect of RNA silencing on inflammation and oxidative stress was studied in human monocytic THP-1 cells. RESULTS: Interleukin-1 receptor-associated kinase-3 (IRAK3), key inhibitor of IRAK/NFκB-mediated chronic inflammation, is downregulated in monocytes of obese persons. Low IRAK3 was associated with high superoxide dismutase-2 (SOD2), a marker of mitochondrial oxidative stress. A comparable expression profile was also detected in visceral adipose tissue of the same obese subjects. Low IRAK3 and high SOD2 was associated with a high prevalence of metabolic syndrome (odds ratio: 9.3; sensitivity: 91%; specificity: 77%). By comparison, the odds ratio of high-sensitivity C-reactive protein, a widely used marker of systemic inflammation, was 4.3 (sensitivity: 69%; specificity: 66%). Weight loss was associated with an increase in IRAK3 and a decrease in SOD2, in association with a lowering of systemic inflammation and a decreasing number of metabolic syndrome components. We identified the increase in reactive oxygen species in combination with obesity-associated low adiponectin and high glucose and interleukin-6 as cause of the decrease in IRAK3 in THP-1 cells in vitro. CONCLUSION: IRAK3 is a key inhibitor of inflammation in association with obesity and metabolic syndrome. Our data warrant further evaluation of IRAK3 as a diagnostic and prognostic marker, and as a target for intervention

An investigation of the impacts of climate change on wave energy generation: The Wave Hub, Cornwall, UK

In this paper a generic methodology is presented that allows the impacts of climate change on wave energy generation from a wave energy converter (WEC) to be quantified. The methodology is illustrated by application to the Wave Hub site off the coast of Cornwall, UK. Control and future wave climates were derived using wind fields output from a set of climate change experiments. Control wave conditions were generated from wind data between 1961 and 2000. Future wave conditions were generated using two IPCC wind scenarios from 2061 to 2100, corresponding to intermediate and low greenhouse gas emissions (IPCC scenarios A1B and B1 respectively). The quantitative comparison between future scenarios and the control condition shows that the available wave power will increase by 2–3% in the A1B scenario. In contrast, the available wave power in the B1 scenario will decrease by 1–3%, suggesting, somewhat paradoxically, that efforts to reduce greenhouse gas emissions may reduce the wave energy resource. Meanwhile, the WEC energy will yield decrease by 2–3% in both A1B and B1 scenarios, which is mainly due to the relatively low efficiency of energy extraction from steeper waves by the specific WEC considered. Although those changes are relatively small compared to the natural variability, they may have significance when considered over the lifetime of a wave energy farm. Analysis of downtime under low and high thresholds suggests that the distribution of wave heights at the Wave Hub will have a wider spread due to the impacts of climate change, resulting in longer periods of generation loss. Conversely, the estimation of future changes in joint wave height-period distribution provides indications on how the response and power matrices of WECs could be modified in order to maintain or improve energy extraction in the future

PPAR Agonist-Induced Reduction of Mcp1 in Atherosclerotic Plaques of Obese, Insulin-Resistant Mice Depends on Adiponectin-Induced Irak3 Expression

Synthetic peroxisome proliferator-activated receptor (PPAR) agonists are used to treat dyslipidemia and insulin resistance. In this study, we examined molecular mechanisms that explain differential effects of a PPARα agonist (fenofibrate) and a PPARγ agonist (rosiglitazone) on macrophages during obesity-induced atherogenesis. Twelve-week-old mice with combined leptin and LDL-receptor deficiency (DKO) were treated with fenofibrate, rosiglitazone or placebo for 12 weeks. Only rosiglitazone improved adipocyte function, restored insulin sensitivity, and inhibited atherosclerosis by decreasing lipid-loaded macrophages. In addition, it increased interleukin-1 receptor-associated kinase-3 (Irak3) and decreased monocyte chemoattractant protein-1 (Mcp1) expressions, indicative of a switch from M1 to M2 macrophages. The differences between fenofibrate and rosiglitazone were independent of Pparγ expression. In bone marrow-derived macrophages (BMDM), we identified the rosiglitazone-associated increase in adiponectin as cause of the increase in Irak3. Interestingly, the deletion of Irak3 in BMDM (IRAK3(−/−) BMDM) resulted in activation of the canonical NFκB signaling pathway and increased Mcp1 protein secretion. Rosiglitazone could not decrease the elevated Mcp1 secretion in IRAK3(−/−) BMDM directly and fenofibrate even increased the secretion, possibly due to increased mitochondrial reactive oxygen species production. Furthermore, aortic extracts of high-fat insulin-resistant LDL-receptor deficient mice, with lower adiponectin and Irak3 and higher Mcp1, showed accelerated atherosclerosis. In aggregate, our results emphasize an interaction between PPAR agonist-mediated increase in adiponectin and macrophage-associated Irak3 in the protection against atherosclerosis by PPAR agonists